miRNA2045p靶向RAB2A调控胶质瘤增殖 迁移与侵袭的机制分析.docx

北京协和医学院博士研究生学位论文 移植模型的影响。结果显示miR．204．5p过表达可以明显抑制胶质瘤的生长，减少 Ki．67的阳性表达，从而延长小鼠的生存时间。 本研究从临床水平、体外细胞水平和体内动物水平上探讨了miR．204．5p在胶质 瘤中的生物学，验证了RAB22A为miR．204．5p的直接调控靶基因，其在miR．204．5D 的胶质瘤细胞生长调控中发挥了重要作用，也为以后更深入地研究miR．204．5p的功 能提供了重要的线索。 关键词：胶质瘤；miRNA；qRT．PCR；RAB22A；裸鼠原位移植模型 万方数据  ABS。I’RACT High—grade gliomas are the most common form of adult malignant braill tumors． and are characterized by rapid progression，high resistance to radiotherapv or chemotherapy，as well as exhibit extremely poor clinical prognosis．Similar to otller tumors-glioma mainly results from genetic risk factors and environmental carcinogenic factors·Some genetic diseases，environmental carcinogenic factors may also be associated with the occurrence of glioma．Consequently，a better understanding of the molecular mechanisms involving glioma formation and development will be helpful to highlight novel therapeutic targets and develop strategies for the trea缸11ent of gliomas． miRNA is a class of non coding single stranded small molecule RNA with 5 tend band with phosphoric acid group of 20-24 nucleotides，and 3’end band with hydroxyl． miRNAs have emerged as key factors involved in several biological processes，includ啦 development，differentiation,cell proliferation，and tumorigenesis．The dysregulation of miRNAs in cancer has been repeatedly described，miRNAs is also inv01ved in the pathological process of many malignant tumors，and the abnormal expression of miRNA is also related to the glioma．miR一204 is one of the most common abnornlal changes of miRNA，miR-204 in the mature process can be divided the miR．204．5p and miR．204．5D． miR_204-5p has been reported to function as a tulnor suppressor in a variety of h啪an cancers through different mechanisms，suggesting its extensive function in turnor stage。 lymph node metastasis，poor prognosis．However，the role of miR．204．5p in glioma was not well known．RAB22A is usually activated by binding GTP in the transport vesicles and then hydrolysed to generate GDP-bound RABs after membra